Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia (original) (raw)
- Letter
- Published: 02 September 1993
- Laura Blinderman1,
- Kelly A. Combs2,
- Bernadette Kienzle1,
- Beverly Ricci1,
- Karen Wager-Smith1,
- Cleris M. Gil2,
- Christoph W. Turck3,
- Marie-Elizabeth Boumas4,
- Daniel J. Rader5,
- Lawrence P. Aggerbeck6,
- Richard E. Gregg1,
- David A. Gordon1 &
- …
- John R. Wetterau1
Nature volume 365, pages 65–69 (1993)Cite this article
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Abstract
THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospho-lipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent _M_r of 88K (refs 1–3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and intestine4. The large subunit of MTP was not detectable in four unrelated subjects with abetalipoproteinaemia5, a rare autosomal recessive disease characterized by a defect in the assembly or secretion of plasma lipoproteins that contain apolipo-protein B (ref. 6). We report here the isolation and sequencing of complementary DNA encoding the large subunit of MTP. A comparison of this sequence to corresponding genomic sequences from two abetalipoproteinaemic subjects revealed a homozygous frameshift mutation in one subject and a homozygous nonsense mutation in the other. The results indicate that a defect in the gene for the large subunit of MTP is the proximal cause of abetalipopro-teinaemia in these two subjects, and that MTP is required for the secretion of plasma lipoproteins that contain apolipoprotein B.
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References
- Wetterau, J. R. & Zilversmit, D. B. Chem. Phys. Lipids 38, 205–222 (1985).
Article CAS Google Scholar - Wetterau, J. R., Combs, K. A., Spinner, S. N. & Joiner, B. J. J. biol. Chem. 265, 9800–9807 (1990).
CAS PubMed Google Scholar - Wetterau, J. R., Aggerbeck, L. P., Laplaud, P. M. & McLean, L. R. Biochemistry 30, 4406–4412 (1991).
Article CAS Google Scholar - Wetterau, J. R. & Zilversmit, D. B. Biochim. biophys. Acta 875, 610–617 (1986).
Article CAS Google Scholar - Wetterau, J. R. et al. Science 258, 999–1001 (1992).
Article ADS CAS Google Scholar - Kane, J. P. & Havel, R. J. in The Metabolic Basis of Inherited Disease 6th edn (eds Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) 1139–1164 (McGraw-Hill, New York, 1989).
Google Scholar - Wetterau, J. R., Combs, K. A., McLean, L. R., Spinner, S. N. & Aggerbeck, L. P. Biochemistry 30, 9728–9735 (1991).
Article CAS Google Scholar - Proudfoot, N. J. & Brownlee, G. G. Nature 263, 211–214 (1976).
Article ADS CAS Google Scholar - Von Heijne, G. Eur. J. Biochem. 133, 17–21 (1983).
Article CAS Google Scholar - Schafer, B. L. et al. J. biol. Chem. 267, 13229–13238 (1992).
CAS PubMed Google Scholar - Cianflone, K. M., Yasruel, Z., Rodriguez, M. A., Vas, D. & Sniderman, A. D. J. Lipid Res. 31, 2045–2055 (1990).
CAS PubMed Google Scholar - Dixon, J. L., Furukawa, S. & Ginsberg, H. L. J. biol. Chem. 266, 5080–5086 (1991).
CAS PubMed Google Scholar - White, A. L., Graham, D. L., LeGros, J., Pease, R. J. & Scott, J. J. biol. Chem. 267, 15657–15664 (1992).
CAS PubMed Google Scholar - Sato, R., Imanaka, T., Takatsuki, A. & Takano, T. J. biol. Chem. 265, 11880–11884 (1990).
CAS PubMed Google Scholar - Furukawa, S., Sakata, N., Ginsberg, H. N. & Dixon, J. L. J. biol. Chem. 267, 22630–22638 (1992).
CAS PubMed Google Scholar - Davis, R. A. et al. J. Lipid Res. 30, 1185–1196 (1989).
ADS CAS PubMed Google Scholar - The Expert Panel Arch. intern. Med. 18, 36–69 (1988).
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Authors and Affiliations
- Department of Metabolic Diseases, Bristol-Myers Squibb, Princeton, New Jersey, 08543-4000, USA
Daru Sharp, Laura Blinderman, Bernadette Kienzle, Beverly Ricci, Karen Wager-Smith, Richard E. Gregg, David A. Gordon & John R. Wetterau - Department of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, Ohio, 45267, USA
Kelly A. Combs & Cleris M. Gil - Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, California, 94143, USA
Christoph W. Turck - U327 Institut National de la Sante et de la Recherche Médicale, Faculté de Médicine Xavier Bichat, Paris, 75018, France
Marie-Elizabeth Boumas - Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA
Daniel J. Rader - Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, 91198, France
Lawrence P. Aggerbeck
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Sharp, D., Blinderman, L., Combs, K. et al. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia.Nature 365, 65–69 (1993). https://doi.org/10.1038/365065a0
- Received: 21 April 1993
- Accepted: 12 July 1993
- Issue Date: 02 September 1993
- DOI: https://doi.org/10.1038/365065a0
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